Is diet related to osteoarthritis? A univariable and multivariable Mendelian randomization study that investigates 45 dietary habits and osteoarthritis

BackgroundDiet is a safe intervention for many chronic diseases as a modifiable lifestyle. However, the potential causal effect of many dietary intake habits on the risk of osteoarthritis has not been fully understood. The purpose of this study was to reveal the potential causal relationship of 45 genetically predicted dietary intakes with osteoarthritis and its subtypes.MethodsData on 45 dietary intakes were obtained from the UK Biobank study of approximately 500,000 participants, and data on six osteoarthritis-related phenotypes were obtained from the Genetics of Osteoarthritis Consortium study of 826,690 participants. We performed univariable Mendelian randomization (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses.ResultsIn univariate analyses, 59 potential associations between diet and osteoarthritis were found. After false discovery rate (FDR) correction and sensitivity analyses, 23 reliable causal evidence were identified. In multivariate analyses, controlling separately for the effects of body mass index, total body bone mineral density, and smoking status, eight robust causal relationships remained: Muesli intake was negatively associated with knee osteoarthritis, spine osteoarthritis and total knee replacement. Dried fruit intake had a negative association with osteoarthritis of knee and total knee replacement. Eating cheese may reduce the risk of osteoarthritis in the knee and spine. And alcohol usually taken with meals was associated with a reduced risk of total knee replacement. LDSC analyses showed significant genetic correlations between all exposures and their corresponding outcomes, respectively, in these eight causal relationships.ConclusionEvidence of dietary effects on osteoarthritis is provided in our study, which has important implications for the prevention, management, and intervention of osteoarthritis in common sites through rational dietary modification

Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data

BackgroundDiabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges Tongmai Jiangtang capsule (TMJT) is commonly used for the treatment of DN, albeit its underlying mechanisms of action are still elusive.MethodsThis study retrieved databases to identify the components and collect the targets of TMJT and DN. Target networks were constructed to screen the core components and targets. Samples from the GEO database were utilized to perform analyses of targets and immune cells and obtain significantly differentially expressed core genes (SDECGs). We also selected a machine learning model to screen the feature genes and construct a nomogram. Furthermore, molecular docking, another GEO dataset, and Mendelian randomization (MR) were utilized for preliminary validation. We subsequently clustered the samples based on SDECG expression and consensus clustering and performed analyses between the clusters. Finally, we scored the SDECG score and analyzed the differences between clusters.ResultsThis study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (CD40LG, EP300, IL1B, GAPDH, and EGF) which were used to construct a nomogram. MR analysis indicated a causal link between elevated IL1B levels and an increased risk of DN. Clustering analysis divided DN samples into four groups, among which, C1 and CI were mainly highly expressed and most immune cells were up-regulated. C2 and CII were the opposite. Finally, we found significant differences in SDECG scores between C1 and C2, CI and CII, respectively.ConclusionTMJT may alleviate DN via core components (e.g. Denudatin B, hancinol, hirudinoidine A) targeting SDECGs (e.g. SRC, EGF, GAPDH), with the involvement of feature genes and modulation of immune and inflammation-related pathways. These findings have potential implications for clinical practice and future investigations

Segmental femoral fracture malunion: evidence and prognostic analysis of medical intervention in the third century BC

Abstract We examined the remains of an individual who was unearthed from the Tuchengzi site and was believed to be from the Warring States period in China. The remains exhibited segmental femoral fracture. We aimed to deduce the cause of fracture, medical interventions, healing process, and motion behavior after fracture healing using several techniques, including macroscopic observation, computed tomography (CT), and finite element analysis. Based on the morphology of the long bones, it appeared that the individual was male. The fractures resulted in an adduction angle of 5.47° and an anterior flexion angle of 21.34° in the proximal femur, while the femoral neck anteversion angle had been replaced by a retroversion angle of 10.74°. Additionally, the distal femur formed an abnormal anterior convex angle of 144.60°. CT revealed mature callus formation and visible trabecular bundles. The finite element analysis indicated that the maximum von Mises stress in the femur was 17.44 MPa during standing and 96.46 MPa during walking. We suggest that medical practitioners in the Warring States period possessed a good knowledge of thigh anatomy, enabling them to perform fracture reduction and fixation. Reasonable medical intervention facilitated fracture healing and load recovery. Satisfactory fracture healing ensured that the individual could engage in normal standing and walking activities after rehabilitation